In Subfertile Couple, Abdominal Fat Loss in Men Is Associated with Improvement of Sperm Quality and Pregnancy: A Case-Series

International audienceBackground: The impact of overweight among men of reproductive-age may affect fertility. Abdominal fat, more than body mass index, is an indicator of higher metabolic risk, which seems to be involved in decreasing sperm quality. This study aims to assess the relationship between abdominal fat and sperm DNA fragmentation and the effect of abdominal fat loss, among 6 men in subfertile couples. Methods: Sperm DNA fragmentation, abdominal fat and metabolic and hormonal profiles were measured in the 6 men before and after dietary advices. Seminal oxidative stress and antioxidant markers were determined. Results: After several months of a lifestyle program, all 6 men lost abdominal fat (patient 1: loss of 3 points of abdominal fat, patient 2: loss of 3 points, patient 3: loss of 2 points, patient 4: loss of 1 point, patient 5: loss of 4 points and patient 6: loss of 13 points). At the same time, their rate of sperm DNA fragmentation decreased: 9.5% vs 31%, 24% vs 43%, 18% vs 47%, 26.3% vs 66%, 25.4% vs 35% and 1.7% vs 25%. Also, an improvement in both metabolic (significant decrease in triglycerides and total cholesterol; p = 0.0139) and hormonal (significant increase in testosterone/oestradiol ratio; p = 0.0139) blood profiles was observed after following the lifestyle program. In seminal plasma, the amount of SOD2 has significantly increased (p = 0.0139) while in parallel carbonylated proteins have decreased. Furthermore, all spouses got pregnant. All pregnancies were brought to term. Conclusion: This study shows specifically that sperm DNA fragmentation among men in subfertile couples could be affected by abdominal fat, but improvement of lifestyle factor may correct this alteration. The effect of specific abdominal fat loss on sperm quality needs further investigation. The reduction of oxidative stress may be a contributing factor

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Soutien de la phase lutéale par les agonistes de la GnRH lors des cycles d hyperstimulation contrôlée en protocole antagoniste

PARIS7-Xavier Bichat (751182101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

STIMULATION OVARIENNE CHEZ DES FEMMES INFERTILES N'AYANT QU'UNE SEULE TROMPE SAINE

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Intérêt d'une supplémentation en LH recombinante humaine dans un protocole utilisant les antagonistes de la GnRH en FIV / ICSI

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

The impact of ovulation induction and ovarian stimulation on the risk of pregnancy-induced hypertension and on neonatal outcomes: A case/ control study

International audienceObjectives: To study the role of ovarian stimulation procedures on the risk of pregnancy-induced hypertension, gestational diabetes mellitus and neonatal outcomes according to women's characteristics and the causes of infertility. Design: Retrospective, observational, case/control study. Patients: Spontaneous pregnancies (group A, n = 8107), pregnancies achieved after mild ovarian ovulation induction without other Assisted Reproductive Technology (ART) procedures (group B, n =44), pregnancies after mild ovarian stimulation and ART procedures (group C, n=53) or pregnancies after multi (>2) follicular stimulation with gonadotrophin therapy and ART procedures (group D, n = 133); all of the groups had identical protocols for prenatal care. Main outcome measurements: Pregnancy-induced hypertension (PIH), fetal macrosomia (estimated fetal weight >90th percentile), gestational diabetes mellitus, caesarean section, and neonatal outcomes. Results: The incidence rates of PIH (2.7,11.6,4.2, and 2.5%) in groups A, B, C and D, respectively, (p = 0.004), fetal macrosomia (4.7, 7.0, 20.8, and 7.6%, respectively, p <0.001), caesarean section (21.8,37.2, 21.7, and 17.6%, respectively, p = 0.048), differed among the groups. The high incidence of PIH in pregnancies following ovulation induction was driven by polycystic ovarian syndrome (PCOS) per se. Conclusion: PCOS per se was associated with more PIH, and ART procedures after mild mono/bi follicular ovarian stimulation were associated with more fetal macrosomia

Should metaphase 1 and 2 stages oocytes be vitrified in the same time for fertility preservation?

Aims: Could metaphase 1 (M1) and 2 (M2) stages oocytes from in vitro maturation (IVM) cycles and controlled-ovarian hyperstimulation (COH) cycles be frozen at the same time without any adverse effect of vitrification on further survival (SR) and maturation rates (MR)? Materials & methods: M1 from cancer patients were prospectively included in IVM/COH groups, and in study or control subgroups if they were vitrified or not. In each study subgroup, SR were compared with that of M2 oocytes vitrified/warmed from egg donors. MR were compared with those of fresh-M1 oocytes from control IVM/COH subgroups. Results: SR were not different between groups. MR compared respectively between survived-and fresh-M1 oocytes were similar when resulting from COH (85.2 vs 81.1%) but significantly lower after IVM (39.1 vs 73.3%). Conclusion: Simultaneous freezing of M1/M2 oocytes could be applied to COH but not to IVM during the course of fertility preservation

Addition of dydrogesterone to vaginal progesterone and transfer postponement improve outcomes in patients with low progesterone levels in hormonally substituted cycles for frozen-thawed embryo transfer

Purpose: Adding dydrogesterone (DYD) to vaginal micronized progesterone (VMP) and postponing embryo transfer in order to improve outcomes in patients with low progesterone (P) levels in hormonally substituted cycles prior to frozen/thawed embryo transfer (FET).&nbsp;Methods: Endometrial preparation comprised sequential administration of vaginal estradiol until endometrial thickness reached 7 mm, followed by transdermal estradiol combined with 800 mg/day VMP. Our previous analysis of serum P levels on FET day showed that the optimal P level was &gt; 11 ng/mL for live birth. Serum P was measured on day1 (D1) following exogenous VMP introduction in the evening. When P levels were &gt; 11 ng/mL, FET was performed &ldquo;in phase&rdquo; on day-2, day-3, or day-5 depending on embryo stage at cryopreservation (n = 139 cycles). When P levels were &lt; 11 ng/mL, DYD 10 mg three times a day orally, was added to VMP and FET was postponed by one day (n = 237 cycles, 63%). The primary endpoint was the comparison of live birth rates (LBR) between the two groups.Results: Mean serum P level on D1 was 10.2 + 3.7 ng/mL. Characteristics of patients in both groups were similar for age, body mass index, endometrial thickness prior to P introduction, quality of transferred embryos, and embryo transfer stage. Regarding the primary endpoint, LBR was similar between the VMP+DYD group and the VMP group (26.1% vs. 27.3%, NS).&nbsp;Conclusion: These results suggest that adding DYD to VMP and postponing the transfer in patients with low P levels in hormonally substituted FET cycles might optimize outcomes

Hypertensive pathologies and egg donation pregnancies: Results of a large comparative cohort study

International audienceObjective: To determine whether egg donation (ED) pregnancies are at higher risk of pregnancy-induced hypertension (PIH) than those achieved by autologous assisted reproductive technology (ART; controls). Design: Anonymous comparative observational matched cohort study. Setting: Assisted reproductive technology centers. Patient(s): Two hundred seventeen ED and 363 control singleton pregnancies matched at 7-8 weeks (pregnancy date, parity, cycle type [fresh/frozen] and women's age). According to French practice, all women were under 45. Intervention(s): None. Main Outcome Measure(s): Percentage of PIH for ED versus controls. Result(s): The groups were comparable (mean age, 34.5). PIH was more frequent during ED pregnancies (17.8% vs. 5.3%), as was preeclampsia (11.2% vs. 2.8%) and eclampsia (1.8% vs. 0.0%). In multivariate analyses, PIH risk increased with ED (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.93-7.97) and women's age (OR, 1.08; 95% CI, 1.00-1.16). No significant effect of previous pregnancies or cycle rank/type was observed. Conclusion(s): This study had sufficient power to detect doubling of the PIH rate. It was demonstrated that the risk of PIH was tripled for ED versus controls. Even in young women, ED is a risk factor for PIH. An immunological explanation seems most likely, that is, the fetus is fully allogeneic to its mother. This risk must be acknowledged to inform couples and provide careful pregnancy monitoring. (C) 2016 by American Society for Reproductive Medicine